Direct measurement of forces between molecules in condensed arrays show a dominating contribution from water structuring. Now measurements of the osmotic sensitivity of DNA-protein and DNA-drug complex formation in dilute solution are also showing a link between binding strength and structured water release. Binding constants for the specific association of galactose repressor with operator and for nonspecific binding differ by a factor of 10/4. This difference is reflected in the release of some 150 water molecules for operator binding compared with nonspecific association. Even much smaller binding energy differences of repressor to different operator sequences are seen as differences in water release. The binding constant of the gal repressor-O/E operator association is twice that of the repressor-O/I complex and is accompanied by the relative release of 6 water molecules. A connection between energy and water release is also seen for drug-DNA interactions. The binding constant of netropsin to an Eco RI site is 10 times stronger than to an Nde I site and also releases some 30 more water molecules. An important role for a change in hydration accompanying a nucleic acid conformational transition has been uncovered. The sensitivity of the B-Z transition to water activity indicates that a difference in the number of solute excluding water molecules between the two conformations is central to the transition. Conditions in the cell may be sufficiently crowded to allow the Z-form to exist without other stresses. Changes in the internal flexibility of Acanthamoeba myosin II minifilaments with ATP binding have been further characterized. Minifilaments with bound ATP are about 50 fold more flexible than with either no bound nucleotide or bound ADP. Changes in flexibility are apparently concomitant with the force generating step. Bending relaxation times extracted the electric birefringence curves indicate that flexing is occurring at the S1-S2 junction. Coupled with our previous experiments, a previously unsuspected tight coupling of the HMM- LMM and the S1-S2 junction conformations probably exists.